Dimethylfurancarboxyanilide derivatives

ABSTRACT

A dimethylfurancarboxyanilide compound of the formula (I):                    
     wherein R 1  and R 2  are the same or different and each is hydrogen, (C 2 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 3 -C 6 )-alkenyl, (C 2 -C 6 ) alkynyl, (C 1 -C 3 )-halogenoalkyl, (C 2 -C 6 )-alkoxy, (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkyl, cyano, substituted amide, (C 1 -C 6 )-alkoxy-carbonyl, benzoyl which is unsubstituted or has 1 to 2 substituents, benzoylamino which is unsubstituted or has 1 to 2 substituents; (C 2 -C 6 )-alkanoylamino, (C 3 -C 6 )-cycloalkylcarbonylamino, benzyl which is unsubstituted or has 1 to 2 substituents, phenyl which is unsubstituted or has 1 to 2 substituents, or (C 1 -C 6 )-alkoxycarbonyl-(C 2 -C 5 )-alkenylene; and R 1  and R 2  do not both represent hydrogen at the same time. A wood preservative containing the dimethylfurancarboxyanilide compound as an active ingredient. A method of preserving wood by applying the dimethylfurancarboxyanilide compound to wood. A wood preservative composition in which the dimethylfurancarboxyanilide compound is combined with at least one of 3-bromo-2,3-diiodo-2-propenylethylcarbamate, 3-iodo-2-propynylbutylcarbamate and 4-chlorophenyl-3-iodopropargylformal.

This is a divisional application of application Ser. No. 09/729,546,filed Dec. 4, 2000 (U.S. Pat. No. 6,380,247), which is a continuationapplication of application Ser. No. 09/306,170, filed May 6, 1999(abandoned), which is a divisional application of application Ser. No.08/999,547 filed Dec. 29, 1997 (U.S. Pat. No. 5,977,168), which is acontinuation-in-part application of Ser. No. 08/730,751 filed Oct. 15,1996 (abandoned), which is a continuation application of Internationalapplication PCT/JP94/00631 (not published in English), filed Apr. 15,1994.

BACKGROUND OF THE INVENTION

1. Technological Field

The present invention is concerned with noveldimethylfurancarboxyanilide derivatives exhibiting an excellentantimicrobial effect, a wood preservative containing thedimethylfurancarboxyanilide derivative as the active ingredient, and awood preservative composition in which the dimethylfurancarboxyanilidederivative as one of the active ingredients is combined with anycommercially available wood preservative the effect of which has beenalready confirmed.

2. Background Technology

Various kinds of inorganic or organic compounds have previously beenemployed to preserve timber against decay due to various wood-rottingfungi. However, these chemicals have faults such as affecting the humanbody because of their high toxicity, showing environmental polution,requiring a high concentration thereof when employed and beingexpensive.

As for compounds relating to the dimethylfurancarboxyanilide derivativesof the present invention, compounds represented by the formula belowhave been disclosed in Japanese Patent Kokai Application Sho 50-10376 asa chemical for preventing plant injury; in which, however, R is limitedto phenyl, nitro-substituted phenyl, carboxy-substituted phenyl,phenyl-substituted phenyl, methyl-substituted phenyl,halogen-substituted phenyl or methoxy-substituted phenyl. In addition,this patent is silent on the other derivatives, and no activity of thesecompounds on wood-rotting fungi has been described.

SUMMARY OF THE INVENTION

The object of the present invention exists in providing a novel woodpreservative which is safer, and is possible to use effectively at a lowconcentration and/or at a low price.

In consideration of such situation as mentioned above, the presentinventors considered furancarboxyanilide derivatives, and studiedeagerly. Our study resulted in finding that noveldimethylfurancarboxyanilide derivatives represented by the generalformula (I) below are very useful as a wood preservative andfurthermore, if the dimethylfurancarboxyanilide derivative as the activeingredient is combined with any other commercially available woodpreservative, potentiation effect can be observed and a woodpreservative composition can be prepared.

The compounds of the present invention are thedimethylfurancarboxyanilide derivatives represented by the generalformula

In this formula, R¹ and R² are the same or different and each representshydrogen atom; an alkyl group having from 2 to 6 carbon atoms; acycloalkyl group having from 3 to 6 carbon atoms; an alkenyl grouphaving from 3 to 6 carbon atoms; an alkynyl group having from 2 to 6carbon atoms; a halogenoalkyl group having from 1 to 3 carbon atoms; analkoxy group having from 2 to 6 carbon atoms; an alkoxyalkylene grouphaving from 1 to 6 carbon atoms in the alkoxy moiety and having from 1to 6 carbon atoms in the alkylene moiety; a cyano group; a substitutedamide group; an alkoxycarbonyl group having from 1 to 6 carbon atoms inthe alkoxy moiety; a benzoyl group which may have optionally from 1 to 2substituents; a benzoylamino group which may have optionally from 1 to 2substituents; an alkanoylamino group having from 2 to 6 carbon atoms; acycloalkylcarbonylamino group having from 3 to 6 carbon atoms in thecycloakyl moiety; a benzyl group which may have optionally from 1 to 2substituents; a phenyl group which may have optionally from 1 to 2substituents; or an alkoxycarbonylalkenylene group having from 1 to 6carbon atoms in the alkoxy moiety and having from 2 to 5 carbon atoms inthe alkenylene moiety; and R¹ and R² do not represent hydrogen atoms atthe same time]. The present invention concerns the compounds mentionedabove, a wood preservative and a wood preservative composition eachcontaining the dimethylfurancarboxyanilide derivative as the activeingredient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A to 1F show the minimum inhibitory concentrations (ppm) ofCompound of Example 20 in combination with various wood preservatives.

FIGS. 2A to 2F show the minimum inhibitory concentrations (ppm) ofCompound of Example 21 in combination with various wood preservatives.

DETAILED DESCRIPTION OF THE INVENTION

In the general formula (I) above, as an alkyl group having from 2 to 6carbon atoms, which is included in the definitions for R¹ and R², theremay be mentioned a straight or branched chain alkyl group such as ethyl,propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl,isopentyl, neo-pentyl, hexyl, isohexyl or sec-hexyl; particularlypreferably an alkyl group having from 2 to 6 carbon atoms.

In the general formula (I) above, as a cycloalkyl group having from 3 to6 carbon atoms, which is included in the definitions for R¹ and R²,there may be mentioned a cycloalkyl group such as cyclopropyl,cyclobutyl, cyclopentyl, or cyclohexyl; preferably a cycloalkyl grouphaving from 3 to 6 carbon atoms; and more preferably a cycloalkyl grouphaving from 5 to 6 carbon atoms.

In the general formula (I) above, as an alkenyl group having from 3 to 6carbon atoms, which is included in the definitions for R¹ and R², theremay be mentioned an alkenyl group such as allyl, isopropenyl, metallyl,2-butenyl, 3-butenyl, 1,3-butandienyl, 2-pentenyl, or 2-hexenyl;preferably an alkenyl group having from 3 to 4 carbon atoms; and morepreferably isopropenyl.

In the general formula (I) above, as an alkynyl group having from 2 to 6carbon atoms, which is included in the definitions for R¹ and R², theremay be mentioned an alkynyl group such as ethynyl, propargyl, 2-butynyl,4-pentynyl, or 2-hexynyl; preferably an alkynyl group having from 2 to 4carbon atoms; and more preferably ethynyl.

In the general formula (I) above, as a halogenoalkyl group having from 1to 3 carbon atoms, which is included in the definitions for R¹ and R²,there may be mentioned a halogenoalkyl group such as trifluoromethyl,trichloromethyl, pentafluoroethyl, 2,2,2-trichloroethyl or2,4-dichloropropyl; preferably a halogenoalkyl group having from 1 to 2carbon atoms; and more preferably trifluoromethyl.

In the general formula (I) above, as an alkoxy group having from 2 to 6carbon atoms, which is included in the definitions for R¹ and R², theremay be mentioned a straight or branched chain alkoxy group such asethoxy, propoxy, isopropoxy, butoxy, pentoxy or hexyloxy; preferably analkoxy group having from 2 to 4 carbon atoms; and more preferably analkoxy group having from 2 to 3 carbon atoms.

In the general formula (I) above, as an alkoxy group having from 1 to 6carbon atoms contained in an alkoxyalkyl group having from 1 to 6 carbonatoms in the alkoxy moiety and having from 1 to 6 carbon atoms in thealkyl moiety, which is included in the definitions for R¹ and R², theremay be mentioned a straight or branched chain alkoxy group such asmethoxy, ethoxy, propoxy, isopropoxy, butoxy, pentoxy, neo-pentoxy orhexyloxy; preferably an alkoxy group having from 1 to 5 carbon atoms;and more preferably an alkoxy group having from 1 to 3 carbon atoms orhaving 5 carbon atoms.

In the general formula (I) above, as an alkylene group contained in analkoxyalkylene group having from 1 to 6 carbon atoms in the alkoxymoiety and from 1 to 6 carbon atoms in the alkylene moiety which isincluded in the definitions for R¹ and R², there may be mentioned astraight or branched chain alkylene group such as methylene, ethylene,propylene, trimethylene, tetramethylene, pentamethylene orhexamethylene; preferably an alkylene group having from 1 to 2 carbonatoms; and more preferably methylene.

In the general formula (I) above, as a substituted amide group, which isincluded in the definitions for R¹ and R², there may be mentioned amonoalkylamide group such as methylamide, ethylamide, isopropylamide,butylamide, sec-butylamide; a dialkylamide group such as dimethylamide,diethylamide, diisopropylamide, dibutylamide, di-sec-butylamide,methylethylamide, methylisopropylamide, methylbutylamide,methyl-sec-butylamide, ethylisopropylamide, isopropylbutylamide,pyrrolidylamide or piperidylamide; an optionally substituted phenylamidesuch as phenylamide, 2-chlorophenylamide, 2,4-dichlorophenylamide,2-methylphenylamide, 2-ethylphenylamide or 4-methoxyphenylamide;preferably methylamide, piperidylamide or phenylamide.

In the general formula (I) above, as an alkoxycarbonyl group having from1 to 6 carbon atoms in the alkoxy moiety, which is included in thedefinitions for R¹ and R², there may be mentioned a group which isformed from the aforementioned alkoxy group having from 1 to 6 carbonatoms contained in an alkoxyalkyl group having from 1 to 6 carbon atomsin the alkoxy moiety and having from 1 to 6 carbon atoms in the alkylmoiety and from a carbonyl group, such as methoxycarbonyl,ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, sec-butoxycarbonyl,tert-butoxycarbonyl, pentyloxycarbonyl or hexyloxycarbonyl; preferablyan alkoxycarbonyl group having from 1 to 3 carbon atoms in the alkoxymoiety.

In the general formula (I) above, as a benzoyl group which may haveoptionally from 1 to 2 substituents, which is included in thedefinitions for R¹ and R², there may be mentioned an optionallysubstituted benzoyl group such as benzoyl, 2-chlorobenzoyl,2,4-dichlorobenzoyl, 2-methylbenzoyl, 2,4-dimethylbenzoyl,4-ethylbenzoyl or 4-methoxybenzoyl; preferably benzoyl.

In the general formula (I) above, as a benzoylamino group which may haveoptionally from 1 to 2 substituents, which is included in thedefinitions for R¹ and R², there may be mentioned an optionallysubstituted benzoylamino group which is formed by substitution of aminogroup(s) to the aforementioned benzoyl group which may have optionallyfrom 1 to 2 substituents such as benzoylamino, 2-chlorobenzoylamino,2,4-dichlorobenzoylamino, 2,4-dimethylbenzoylamino,4-methylbenzoylamino, 4-ethylbenzoylamino or 4-methoxybenzoylamino;preferably benzoylamino.

In the general formula (I) above, as an alkanoylamino group having from2 to 6 carbon atoms, which is included in the definitions for R¹ and R²,there may be mentioned acetylamino, propionylamino, butyrylamino,isobutyrylamino, valerylamino, isovalerylamino, caproylamino orisocaproylamino; preferably acetylamino.

In the general formula (I) above, as a cycloalkylcarbonylamino grouphaving from 3 to 6 carbon atoms in the cycloalkyl moiety, which isincluded in the definitions for R¹ and R², there may be mentionedcyclopropylcarbonylamino, cyclobutylcarbonylamino,cyclopentylcarbonylamino or cyclohexylcarbonylamino; preferablycyclohexylcarbonylamino.

In the general formula (I) above, as a benzyl group which may haveoptionally from 1 to 2 substituents, which is included in thedefinitions for R¹ and R², there may be mentioned benzyl,2-methylbenzyl, 2,4-dimethylbenzyl, 2-chlorobenzyl, 4-methoxybenzyl or4-ethoxybenzyl; preferably benzyl.

In the general formula (I) above, as an alkoxycarbonylalkenylene grouphaving from 1 to 6 carbon atoms in the alkoxy moiety and having from 2to 5 carbon atoms in the alkenylene moiety, which is included in thedefinitions for R¹ and R², there may be mentionedmethoxycarbonylvinylene, ethoxycarbonyl-2-propenylene,methoxycarbonyl-2-butenylene or ethoxycarbonyl-2-pentenylene; preferablymethoxycarbonylvinylene.

Preferred compound having the general formula (I) above include ones inwhich:

(1) R¹ and R² are the same or different and each represents a hydrogenatom; an alkyl group having from 2 to 6 carbon atoms; an alkenyl grouphaving from 3 to 4 carbon atoms; an alkynyl group having from 2 to 4carbon atoms; a cycloalkyl group having from 3 to 6 carbon atoms; analkoxycarbonyl group having from 1 to 6 carbon atoms in the alkoxymoiety; an alkoxyalkylene group having from 1 to 6 carbon atoms in thealkoxy moiety and having from 1 to 2 carbon atoms in the alkylenemoiety; a cycloalkylcarbonylamino group having from 3 to 6 carbon atomsin the cycloalkyl moiety; an alkoxy group having from 2 to 4 carbonatoms; a benzoyl group which may have optionally from 1 to 2substituents; a benzyl group which may have optionally from 1 to 2substituents; or an alkoxycarbonylalkenylene group having from 1 to 6carbon atoms in the alkoxy moiety and having from 2 to 5 carbon atoms inthe alkenylene moiety; and R¹ and R² do not represent hydrogen atoms atthe same time. More preferred ones include those in which:

(2) R¹ and R² are the same or different and each represents a hydrogenatom; an alkyl group having from 2 to 6 carbon atoms; an alkenyl grouphaving from 3 to 4 carbon atoms; a cycloalkyl group having from 5 to 6carbon atoms; an alkoxycarbonyl group having from 1 to 3 carbon atoms inthe alkoxy moiety; an alkoxymethylene group having from 1 to 6 carbonatoms in the alkoxy moiety; a cycloalkylcarbonylamino group having from4 to 6 carbon atoms in the cycloalkyl moiety; a benzoyl group; a benzylgroup which may have optionally 1 substituent; or analkoxycarbonylalkenylene group having from 1 to 3 carbon atoms in thealkoxy moiety and having from 2 to 4 carbon atoms in the alkenylenemoiety; and R¹ and R² do not represent hydrogen atoms at the same time.Particularly preferred ones include those in which:

(3) R¹ is a 3-alkyl group having from 2 to 6 carbon atoms; a3-alkoxycarbonyl group having from 1 to 3 carbon atoms in the alkoxymoiety; a 3-alkoxymethylene group having from 1 to 3 carbon atoms in thealkoxy moiety; a cycloalkylcarbonylamino group having from 4 to 6 carbonatoms in the cycloalkyl moiety; a benzoyl group which may be substitutedby a methoxy group; a benzoyl group; or an alkoxycarbonylalkenylenegroup having from 1 to 3 carbon atoms in the alkoxy moiety and havingfrom 2 to 3 carbon atoms in the alkenylene moiety; and

(4) R² is a hydrogen atom.

Novel dimethylfurancarboxyanilide derivatives which may be used as anactive ingredient of the wood preservative of the present invention areexemplified in the following table.

Bz Benzyl Bu Butyl Et Ethyl Hx Hexyl Me Methyl Ph Phenyl Pip PiperidylPn Pentyl Pr Propyl i iso s secondary t tertiary c cyclo

TABLE 1 Compound No. R¹ R² 1 3-CF₃ H 2 4-CF₃ H 3 3-CH₂OMe H 4 4-CH₂OMe H5 2-Et H 6 3-Et H 7 4-Et H 8 3-C≡CH H 9 4-C≡CH H 10 3-CH₂OEt H 114-CH₂OEt H 12 2-Et 3-Et 13 2-Et 4-Et 14 2-Et 5-Et 15 2-Et 6-Et 16 3-Et4-Et 17 3-Et 5-Et 18 3-Et 6-Et 19 3-Pr H 20 4-Pr H 21 2-iPr H 22 3-iPr H23 4-iPr H 24 3-cPr H 25 4-cPr H 26 3-CH₂OPr H 27 3-CH₂OiPr H 284-CH₂OiPr H 29 3-CH₂C═CH₂ H 30 4-CH₂C═CH₂ H 31 3-CH₂C≡CH H 32 4-CH₂C≡CHH 33 3-Pr 4-Pr 34 2-iPr 4-iPr 35 3-iPr 5-iPr 36 3-CH₂OBu H 37 4-CH₂OBu H38 3-CH₂OiBu H 39 4-CH₂OiBu H 40 3-CH₂OsBu H 41 4-CH₂OsBu H 42 3-Bu H 434-Bu H 44 3-iBu H 45 3-sBu H 46 3-cBu H 47 4-cBu H 48 3-tBu H 493-CH₂CH═CHMe H 50 3-CH₂C≡CMe H 51 3-CH₂MeCH═CH₂ H 52 4-CH₂MeCH═CH₂ H 533-Pn H 54 4-Pn H 55 3-iPn H 56 3-cPn H 57 3-neoPn H 58 3-CH₂OPn H 593-CH₂Oneo-Pn H 60 3-Hx H 61 3-iHx H 62 3-cHx H 63 3-CN H 64 3-OEt H 653-OiPr H 66 3-CONHMe H 67 3-(co-1-Pip) H 68 3-CONHPh H 69 3-COOMe H 703-COOEt H 71 3-COOPr H 72 3-COOiPr H 73 3-COOBu H 74 3-COOtBu H 753-COPh H 76 3-CO(2-MePh) H 77 3-NHCOPh H 78 3-NHCOMe H 79 3-NHCOBu H 803-NHCOcPn H 81 3-NHCOcHx H 82 3-Bz H 83 3-(4-MeOBz) H 84 3-(4-MeBz) H 853-CH═CHCOOMe H 86 3-Ph H 87 3-(2-MePh) H

Among the compounds above, preferred ones include Compound Nos. 3, 4, 5,6, 7, 8, 10, 11, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 31, 33, 35, 36, 38, 40, 42, 43, 44, 45, 46, 48, 49, 50, 51, 53, 54,55, 56, 57, 58, 59, 60, 61, 62, 64, 69, 70, 71, 72, 75, 80, 81, 82, 83and 85; and more preferred ones include Compound Nos. 3, 6, 10, 19, 22,24, 26, 27, 33, 35, 36, 38, 40, 42, 44, 45, 46, 48, 53, 55, 60, 61, 69,70, 81, 83 and 85.

The compounds of the said general formula (I) may be prepared accordingto the procedure summarized in either the following Method A or MethodB.

In the above formulae, R¹ and R² are as defined above. R^(1′) representsa C₁-C₆ alkyl, C₃-C₆ cycloalkyl or benzyl group which may optionallyhave 1 or 2 substituents. The compound of formula (Ia) is that of ageneral formula (I), in which R¹ is R^(1′) and R² signifies a hydrogenatom. The compound of formula (V) is iodine-substituted aniline. Xsignifies a halogen atom such as chlorine, bromine or iodine, preferablychlorine. X′ signifies a halogen atom such as a chlorine, bromine oriodine, preferably bromine or iodine.

The compounds of the present invention may be prepared by well-knownprocedure.

Step A1 consists of the preparation of a compound of general formula (I)by reacting a compound of general formula (III) with a compound ofgeneral formula (IV) in an inert solvent in the presence of adehydrohalogenating agent.

A compound of formula (III) used as a starting material in this step maybe prepared by hydrolyzing 2,5-dimethylfuran-3-carboxylate, which may beprepared by condensing chloroacetone with acetoacetate, followed byhalogenation.

A compound of formula (IV) used as a starting material in this step isan aniline derivative which is commercially available or may be preparedby well-known methods.

Examples of the inert solvents used include, for example, ethers such asether, isopropyl ether, tetrahydrofuran or dioxane; aromatichydrocarbons such as benzene, toluene or xylene; halogenatedhydrocarbons such as dichloromethane, chloroform or carbontetrachloride; and mixtures of two or more of these solvents; preferablyaromatic hydrocarbons (particularly toluene).

Examples of dehydrohalogenating agents used include, for example,tertiary amines such as triethylamine, N,N-dimethylaminopyridine or thelike and pyridines. This reaction can be carried out in the presence orabsence of a solvent. In order to perform the reaction smoothly, using asolvent, the reaction is carried out at a temperature of 0° C. to refluxtemperature of the solvent used, preferably from room temperature to100° C. The time required for the reaction takes generally from 30minutes to 5 hours, preferably from 30 minutes to 2 hours.

Step B1 consists of the preparation of a compound having general formula(VI) by reacting a compound having general formula (III) with a compoundhaving general formula (V) in an inert solvent in the presence of adehydrohalogenating agent.

A compound of formula (IV) used as a starting material in this step isan aniline derivative which is commercially available or may be preparedby well-known methods.

The reaction conditions employed in this step are similar to thoseemployed in Step A1.

Step B2 consists of the preparation of a compound having general formula(Ia) by reacting a compound having general formula (VI) with a Grignardreagent having general formula: R^(1′)MgX′ in an inert solvent in thepresence of a catalyst.

Examples of preferred inert solvents used include, for example, etherssuch as diethyl ether, isopropyl ether, tetrahydrofuran or dioxane;particularly preferably diethyl ether.

As a particularly preferred catalyst there may be used[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride.

The Grignard reagents used in this process are commercially available orcan be prepared by reacting magnesium with an alkyl halide representedby formula: R^(1′)X^(′) (wherein R^(1′) and X′ are as defined above)according to well-known methods.

The reaction is normally carried out at a temperature of 0° C. to 50°C., preferably at room temperature. Although the time required for thereaction varies depending upon the nature of the solvent and reagent tobe used, the reaction is normally complete within a period of 10 hoursto 10 days.

The compounds having the said general formula (I) in according with theinvention have potent wood preservative activity at low concentration,compared with the activity shown by existing wood preservatives. Acomposition consisting of a combination of the foregoing compound (I)with a known wood preservative gives a synergistic effect, lowerconcentrations of each compound being required than would be expectedfrom the activity shown by each singly, such that the composition showsefficient wood preservative activity at a low concentration. Therefore,novel dimethylfurancarboxyanilide derivatives are extremely effective asa wood preservative in low concentration so as to solve one of theproblems in the quality of life.

The following Examples illustrate the preparation and the formulation ofthe compound of the invention in more detail. Such examples are not tobe construed as being limitative of the scope of the invention.

EXAMPLE 1 2,5-Dimethylfuran-3-carboxy(3-acetylaminoanilide)

To a solution of 0.50 g of 2,5-dimethylfuran-3-carbonyl chloride in 10ml of dichloromethane were added 0.44 ml of triethylamine and 0.47 g of3-acetylaminoaniline under ice-cooling, and the resulting mixture wasstirred at room temperature for 2.5 hours followed by heating underreflux for 4.5 hours. After the reaction mixture was cooled, it wasdiluted by adding 10 ml of dichloromethane. The diluted mixture wassuccessively washed with 1 N sodium hydroxide, 1 N hydrochloric acid anda saturated aqueous solution of sodium chloride and dried over sodiumsulfate followed by distilling off the solvent. The residue was purifiedby column chromatography through silica gel and the desired fractionswere recrystallized from ethyl acetate to give 0.51 g of the desiredcompound as white crystals in a 59.4% yield.

m.p.:172.0-172.5° C.

¹H NMR (CDCl₃+DMSO) δ ppm: 8.4 (1H, b), 7.95 (1H, b), 7.88 (1H, m), 7.4(1H, m), 7.32 (1H, m), 7.25 (1H, t, J=8 Hz), 6.25 (1H, s), 2.55 (3H, s),2.25 (3H, s), 2.15 (3H, s)

IR (KBr) cm⁻¹:3306, 1672, 1651, 1086, 781

Elemental analysis (%): Calc'd for C₁₅H₁₆N₂O₃: C, 66.16; H, 5.92; N,10.29. Found: C, 66.30; H, 5.98; N, 10.32.

Following the similar procedure as above, but using an appropriateaniline derivative instead of 3-acetylaminoaniline, there were obtainedthe following compounds.

EXAMPLE 2 2.5-Dimethylfuran-3-carboxy[3-(N-methylcarbamoyl)anilide]

Yield:42.0%

m.p.:212.0-213.0° C.

¹H NMR (CDCl₃+DMSO) δ ppm: 8.5 (1H, b), 8.05 (1H, m), 7.88 (1H, m), 7.52(1H, m), 7.38 (1H, t, J=8 Hz), 6.8 (1H, b), 6.35 (1H, s), 2.95 (3H, d,J=1.4 Hz), 2.55 (3H, s), 2.25 (3H, s).

IR (KBr) cm⁻¹:3293, 1638, 1581, 1074, 689

Elemental analysis (%): Calc'd for C₁₅H₁₆N₂O₃: C, 66.16; H, 5.92; N,10.29. Found: C, 66.08; H, 6.20; N, 10.28.

EXAMPLE 3 2,5-Dimethylfuran-3-carboxy[3-(1-piperidylcarbonyl)anilide]

Yield:50.0%

m.p.:183.0-185.0° C.

¹H NMR spectrum (CDCl₃) δ ppm: 7.68 (1H, m), 7.55 (2H, m), 7.35 (1H, t,J=8 Hz), 7.1 (1H, m), 6.15 (1H, s), 3.7 (2H, b), 3.35 (2H, b), 2.55 (3H,s), 2.25 (3H, s), 2.75−1.4 (6H, m)

IR (KBr) cm⁻¹:3302, 1663, 1615, 1065, 808

Elemental analysis (%): Calc'd for C₁₉H₂₂N₂O₃: C, 69.92; H, 6.79; N,8.58. Found: C, 69.52; H, 6.88; N, 8.48.

EXAMPLE 4 2.5-Dimethylfuran-3-carboxyl[3-(N-phenylcarbamoyl)anilide]

Yield:53.5%

m.p.:182.5-184.0° C.

¹H NMR (CDCl₃+DMSO) δ ppm: 8.48 (1H, b), 8.2 (1H, b), 8.1 (1H, s), 7.95(1H, m), 7.7 (2H, d, J=8 Hz), 7.65 (1H, d, J=8 Hz), 7.45 (1H, t, J=8Hz), 7.35 (2H, t, J=8 Hz), 7.15 (1H, t, J=8 Hz), 6.28 (1H, s), 2.55 (3H,s), 2.25 (3H, s)

IR (KBr) cm⁻¹:3282, 1646, 1080, 755, 691

Elemental analysis (%): Calc'd for C₂₀H₁₈N₂O₃: C, 71.84; H, 5.43; N,8.38. Found: C, 71.87; H, 5.64; N, 8.34.

EXAMPLE 5 2,5-Dimethylfuran-3-carboxy(3-tert-butoxycarbonylanilide)

Yield:92.0%

m.p.:117.0-118.0° C.

¹H NMR (CDCl₃) δ ppm: 8.05 (1H, m), 7.88 (1H, m), 7.75 (1H, m), 7.4 (1H,t, J=8 Hz), 7.35 (1H, b), 6.1 (1H, s), 2.55 (3H, s), 2.25 (3H, s), 1.65(9H, s)

IR (KBr) cm⁻¹:3362, 1687, 1672, 1067, 757

Elemental analysis (%): Calc'd for C₁₈H₂₁NO₄: C, 68.55; H, 6.71; N,4.44. Found: C, 68.04; H, 7.00; N, 4.40.

EXAMPLE 6 2,5-Dimethylfuran-3-carboxy(3-methoxycarbonylanilide)

Yield:77.1%

m.p.:104.0-106.0° C.

¹H NMR (CDCl₃) δ ppm: 8.05 (1H, m), 7.98 (1H, m), 7.8 (1H, m), 7.42 (1H,t, J=8 Hz), 7.38 (1H, b), 6.1 (1H, s), 3.92 (3H, s), 2.55 (3H, s), 2.25(3H, s)

IR (KBr) cm⁻¹:3437, 1704, 1675, 1070, 759

Elemental analysis (%): Calc'd for C₁₅H₁₅NO₄: C, 65.92; H, 5.53; N,5.13. Found: C, 66.02; H, 5.60; N, 5.08.

EXAMPLE 7 2,5-Dimethylfuran-3-carboxy(3-benzoylanilide)

Yield:69.1%

m.p.:137.0-139.0° C.

¹H NMR (CDCl₃) δ ppm: 8.05 (1H, m), 7.85−7.7 (3H, m), 7.6 (1H, m),7.55−7.35 (5H, m), 6.1 (1H, s), 2.55 (3H, s), 2.25 (3H, s)

IR (KBr) cm⁻¹:3386, 1672, 1647, 1069, 707

Elemental analysis (%): Calc'd for C₂₀H₁₇NO₃: C, 75.22; H, 5.37; N,4.39. Found: C, 75.38; H, 5.43; N, 4.38.

EXAMPLE 8 2,5-Dimethylfuran-3-carboxy(3-benzoylaminoanilide)

Yield:46.0%

m.p.:194.5-195.0° C.

¹H NMR (CDCl₃+DMSO) δ ppm: 8.7 (1H, b), 8.1 (1H, m), 7.95 (1H, b), 7.9(2H, m), 7.6−7.4 (5H, m), 7.3 (1H, t, J=8 Hz), 6.25 (1H, s), 2.55 (3H,s), 2.25 (3H, s)

IR (KBr) cm⁻¹ 3283, 1642, 1074, 791, 705

Elemental analysis (%): Calc'd for C₂₀H₁₈N₁O₃: C, 71.84; H, 5.43; N,8.38. Found: C, 71.96; H, 5.53; N, 8.28.

EXAMPLE 9 2,5-Dimethylfuran-3-carboxy(3-valerylaminoanilide)

Yield:70.3%

m.p.:104.0-105.0° C.

¹H NMR (CDCl₃) δ ppm: 7.9 (1H, b), 7.45−7.1 (5H, m), 6.1 (1H, s), 2.55(3H, s), 2.35 (2H, t, J=7 Hz), 2.25 (3H, s), 1.7 (2H, m), 1.4 (2H, m),0.95 (1H, t, J=7 Hz)

IR (KBr) cm⁻¹:3250, 1660, 1644, 1074, 781

Elemental analysis (%): Calc'd for C₁₈H₂₂N₂O₃: C, 68.77; H, 7.05; N,8.91. Found: C, 68.73; H, 7.17; N, 8.90.

EXAMPLE 10 2,5-Dimethylfuran-3-carboxy(3-cyclohexylcarbonylaminoanilide)

Yield:45.1%

m.p.:212.5-213.0° C.

¹H NMR (CDCl₃) δ ppm: 7.92 (1H, b), 7.88 (1H, b), 7.45−7.35 (2H, m),7.25 (1H, t, J=8 Hz), 6.22 (1H, s), 2.55 (3H, s), 2.25 (3H, s), 2.25−2.2(1H, m), 2.0−1.2 (10H, m)

IR (KBr) cm⁻¹:3238, 1651, 1639, 1076, 781

Elemental analysis (%): Calc'd for C₂₀H₂₄N₂O₃: C, 70.57; H, 7.11; N,8.23. Found:C, 70.56; H, 7.26; N, 8.16

EXAMPLE 11 2,5-Dimethylfuran-3-carboxy(3-methoxymethylanilide)

Yield:73.3%

m.p.:102.5-103.5° C.

¹H NMR (CDCl₃) δ ppm: 7.55 (1H, m), 7.52 (1H, d, J=8 Hz), 7.32 (1H, t,J=8 Hz), 7.32 (1H, b), 6.9 (1H, d, J=8 Hz), 6.1 (1H, s), 4.45 (2H, s),3.4 (3H, s), 2.55 (3H, s), 2.25 (3H, s)

IR (KBr) cm⁻¹:3278, 1645, 1237, 1107, 784

Elemental analysis (%): Calc'd for C₁₅H₁₇NO₃: C, 69.48; H, 6.61; N,5.40. Found: C, 69.22; H, 7.02; N, 5.37.

EXAMPLE 12 2,5-Dimethylfuran-3-carboxy(3-ethoxymethylanilide)

Yield:64.4%

m.p.:85.0-85.5° C.

¹H NMR (CDCl₃) δ ppm: 7.65−7.55 (2H, m), 7.38 (1H, t, J=8 Hz), 7.35 (1H,b), 7.15 (1H, d, J=8 Hz), 6.15 (1H, s), 4.55 (2H, s), 3.58 (2H, q, J=8Hz), 2.55 (3H, s), 2.25 (3H, s), 1.3 (3H, t, J=8 Hz)

IR (KBr) cm⁻¹:3279, 1646, 1115, 785

Elemental analysis (%): Calc'd for C₁₆H₁₉NO₃: C, 70.31; H, 7.01; N,5.12. Found: C, 70.14; H, 7.27; N, 5.06.

EXAMPLE 13 2,5-Dimethylfuran-3-carboxy(3-isopropyloxymethylanilide)

Yield:92.7%

m.p.:68.0-69.5° C.

¹H NMR (CDCl₃) δ ppm: 7.55 (1H, d, J=8 Hz), 7.5 (1H, m), 7.3 (1H, t, J=8Hz), 7.3 (1H, b), 7.12 (1H, d, J=8 Hz), 6.1 (1H, s), 4.5 (2H, s), 3.7(1H, m), 2.55 (3H, s), 2.25 (3H, s), 1.25 (6H, d, J=7 Hz)

IR (Liquid film) cm⁻¹:3321, 1651, 1072, 785

Elemental analysis (%): Calc'd for C₁₇H₂₁NO₃: C, 71.06; H, 7.37; N,4.87. Found: C, 70.35; H, 7.14; N, 4.91.

EXAMPLE 14 2,5-Dimethylfuran-3-carboxy[3-(4-methoxybenzyl)anilide]

Yield:86.8%

m.p.:100.0-102.5° C.

¹H NMR (CDCl₃) δ ppm: 7.45 (1H, m), 7.35 (1H, m), 7.25 (1H, t, J=8 Hz),7.25 (2H, b), 7.1 (2H, d, J=8 Hz), 6.92 (1H, d, J=8 Hz), 6.88−6.75 (1H,m), 6.82 (2H, d, J=8 Hz), 6.05 (1H, s), 3.9 (2H, s), 3.75 (3H, s), 2.55(3H, s), 2.25 (3H, s)

IR (KBr) cm⁻¹:3345, 1656, 1246, 1074, 694

Elemental analysis (%): Calc'd for C₂₁H₂₁NO₃: C, 75.20; H, 6.31; N,4.18. Found: C, 75.28; H, 6.32; N, 4.21.

EXAMPLE 152,5-Dimethylfuran-3-carboxy[3-(2-methoxycarbonylvinyl)anilide]

Yield:63.3%

m.p.:159.5-161.5° C.

¹H NMR (CDCl₃) δ ppm: 7.82 (1H, m), 7.7 (1H, d, J=15 Hz), 7.58 (1H, m),7.38 (1H, b), 7.35 (1H, t, J=8 Hz), 7.28 (1H, m), 6.48 (1H, d, J=15 Hz),6.12 (1H, s), 3.82 (3H, s), 2.55 (3H, s), 2.25 (3H, s)

IR (KBr) cm⁻¹:3387, 1685, 1670, 1068, 800

Elemental analysis (%): Calc'd for C₁₇H₁₇NO₄: C, 68.22; H, 5.72; N,4.68. Found: C, 67.55; H, 5.64; N, 4.62.

EXAMPLE 16 2,5-Dimethylfuran-3-carboxy(3-phenylanilide)

Yield:50.0%

m.p.:90.0-92.0° C.

¹H NMR (CDCl₃) δ ppm: 7.82 (1H, s), 7.6 (2H, d, J=8 Hz), 7.55 (1H, d,J=8 Hz), 6.48−6.3 (6H, m), 6.12 (1H, s), 2.55 (3H , s), 2.25 (3H, s)

IR (KBr) cm⁻¹:3367, 1646, 1074, 755

Elemental analysis (%): Calc'd for C₁₉H₁₇NO₂: C, 78.33; H, 5.88; N,4.81. Found: C, 78.17; H, 6.00; N, 4.72.

EXAMPLE 17 2,5-Dimethylfuran-3-carboxy(3-neopentyloxymethylanilide)

Yield:50.0%

m.p.:95.5-97.0° C.

¹H NMR (CDCl₃) δ ppm: 7.48 (2H, m), 7.32 (1H, t, J=8 Hz), 7.3 (1H, b),7.12 (1H, d, J=8 Hz), 4.52 (2H, s), 3.12 (2H, s), 2.55 (3H, s), 2.25(3H, s), 0.95 (9H, s)

IR (KBr) cm⁻¹:3324, 1646, 1091, 700

Elemental analysis (%): Calc'd for C₁₉H₂₅NO₃: C, 72.35; H, 7.99; N,4.44. Found: C, 72.38; H, 8.03; N, 4.20.

EXAMPLE 18 2,5-Dimethylfuran-3-carboxy(3-isopropenylanilide)

Yield:50.0%

m.p.:71.0-72.0° C.

¹H NMR (CDCl₃) δ ppm: 7.65 (1H, m), 7.5 (1H, m), 7.3 (1H, b), 7.3 (1H,t, J=8 Hz), 7.22 (1H, m), 6.12 (1H, s), 5.4 (1H, s), 5.1 (1H, s), 2.6(3H, s), 2.55 (3H, s), 2.25 (3H, s)

IR (KBr) cm⁻¹:3275, 1641, 1580, 1078, 790

Elemental analysis (%): Calc'd for C₁₆H₁₇NO₂: C, 75.27; H, 6.71; N,5.49. Found: C, 75.29; H, 6.88; N, 5.48.

EXAMPLE 19 2,5-Dimethylfuran-3-carboxy(3-ethynylanilide)

Yield:50.0%

m.p.:83.0-84.0° C.

¹H NMR (CDCl₃) δ ppm: 7.7 (1H, m), 7.6 (1H, m), 7.32−7.2 (3H, m), 6.1(1H, s), 3.05 (1H, s), 2.55 (3H, s), 2.25 (3H, s)

IR (KBr) cm⁻¹:3245, 1644, 1079, 796

Elemental analysis (%): Calc'd for C₁₅H₁₃NO₂: C, 75.30; H, 5.48; N,5.85. Found: C, 75.50; H, 5.46; N, 5.96.

EXAMPLE 20 2,5-Dimethylfuran-3-carboxy(3-ethylanilide)

Yield:91.0%

m.p.:113-115° C.

Mass (m/z):243 (M⁺), 123.94

¹H NMR (CDCl₃) δ ppm: 7.47−6.95 (4H, m), 6.1 (1H, s), 2.66 (3H, q), 2.60(3H, s), 2.29 (3H, s), 1.25 (3H, t)

EXAMPLE 21 2,5-Dimethylfuran-3-carboxy(3-isopropylanilide)

Yield:84.0%

m.p.:79-80° C.

Mass (m/z):257 (M⁺), 149.135

¹H NMR (CDCl₃) δ ppm: 7.47−6.98 (4H, m), 6.11 (1H, s), 2.91 (1H, q,q),2.60 (3H, s), 2.29 (3H, s), 1.26 (d, 6H)

EXAMPLE 22 2,5-Dimethylfuran-3-carboxy(2,6-diethylanilide)

Yield:85.2%

m.p.:128.0-131.0° C.

Mass (m/z):271 (M⁺), 242.228

¹H NMR (CDCl₃) δ ppm: 7.28−7.12 (3H, m), 6.82 (1H, b), 6.16 (1H, s),2.63 (4H, q), 2.58 (3H, s), 2.31 (3H, s), 1.20 (6H, t)

EXAMPLE 23 2,5-Dimethylfuran-3-carboxy(3-hexylanilide)

(Step 1) To a solution of 3.95 g of 2,5-dimethylfuran-3-carbonylchloride in 60 ml of dichloromethane were added 3.45 ml of triethylamineand 2.99 ml of m-iodoaniline under ice-cooling, and the resultingmixture was stirred at room temperature for 6.5 hours. After thereaction mixture was cooled, it was diluted by adding 50 ml ofdichloromethane. The diluted mixture was successively washed with 1 Nsodium hydroxide, 1 N hydrochloric acid and a saturated aqueous solutionof sodium chloride and dried over sodium sulfate followed by distillingoff the solvent. The residue was subjected to column chromatographythrough silica gel to give 7.64 g of2,5-dimethylfuran-3-carboxy(3-iodoanilide) as pale-yellow crystals in a89.9% yield.

(Step 2) To a solution of 0.68 g of the crystals obtained in Step 1 in 8ml of diethyl ether were added 29.3 mg of[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride and 11 mlof 1 M hexylmagnesium bromide, prepared from hexyl bromide andmagnesium, divided into six equal parts, and the resulting mixture wasstirred at room temperature for 47 hours. After adding 2 N hydrochloricacid to the reaction mixture, the catalyst was filtered off and thefiltrate was extracted with diethyl ether. The extract was successivelywashed with an aqueous solution of sodium bicarbonate and a saturatedaqueous solution of sodium chloride and dried over sodium sulfate. Afterdistilling off the solvent, the residue was purified by chromatographythrough silica gel and then D-ODS-5, YMC-packed column to give 316 mg ofthe desired compound as white crystals in a 52.8% yield.

m.p.:71.5-72.0° C.

¹H NMR (CDCl₃) δ ppm: 7.45 (1H, m), 7.35 (1H, m), 7.25 (1H, b), 7.22(1H, t, J=8 Hz), 6.95(1H, d, J=8 Hz), 6.1 (1H, s), 2.65−2.5 (2H, m),2.55 (3H, s), 2.25 (3H, s), 1.7−1.5 (2H, m), 1.4−1.2 (6H, m), 0.85 (3H,t, J=7 Hz)

IR (KBr) cm⁻¹:3310, 1643, 1077, 788

Elemental analysis (%): Calc'd for C₁₉H₂₅NO₂: C, 76.22; H, 8.42; N,4.68. Found: C, 76.15; H, 8.54; N, 4.55

Following the similar procedure as above, but using an appropriateGrignard reagent instead of hexylmagnesium bromide, there were obtainedthe following compounds.

EXAMPLE 24 2,5-Dimethylfuran-3-carboxy(3-butylanilide)

Yield:36.4%

m.p.:77.0-80.0° C.

¹H NMR (CDCl₃) δ ppm: 7.45 (1H, m), 7.35 (1H, m), 7.25 (1H, b), 7.22(1H, t, J=8 Hz), 6.95 (1H, d, J=8 Hz), 6.1 (1H, s), 2.65−2.55 (2H, m),2.55 (3H, s), 2.25 (3H, s), 1.6 (2H, m), 1.35 (2H, m), 0.92 (1H, t, J=7Hz)

IR (KBR) cm⁻¹:3285, 1646, 1075, 702

Elemental analysis (%): Calc'd for C₁₇H₂₁NO₂: C, 75.25; H, 7.80; N,5.16. Found: C, 75.13; H, 7.87; N, 5.13

EXAMPLE 25 2,5-Dimethylfuran-3-carboxy(3-sec-butylanilide)

Yield:38.1%

m.p.:80.0-81.0° C.

¹H NMR (CDCl₃) δ ppm: 7.4 (1H, m), 7.38 (1H, m), 7.25 (1H, b), 7.22 (1H,t, J=8 Hz), 6.95 (1H, d, J=8 Hz), 6.1 (1H, s), 2.65−2.5 (1H, m), 2.55(3H, s), 2.25 (3H, s), 1.68−1.5 (2H, m), 1.25 (3H, d, J=7 Hz), 0.85 (3H,t, J=7 Hz)

IR (KBr) cm⁻¹:3255, 1647, 1078, 791

Elemental analysis (%): Calc'd for C₁₇H₂₁NO₂: C, 75.25; H, 7.80; N,5.16. Found: C, 75.19; H, 7.68; N, 5.14

EXAMPLE 26 2,5-Dimethylfuran-3-carboxy(3-pentylanilide)

Yield:18.3%

m.p.:97.0-97.5° C.

¹H NMR (CDCl₃) δ ppm: 7.45 (1H, m), 7.35 (1H, m), 7.28 (1H, b), 7.25(1H, t, J=8 Hz), 6.95 (1H, d, J=8 Hz), 6.1 (1H, s), 2.65−2.5 (2H, m),2.55 (3H, s), 2.25 (3H, s), 1.7−1.5 (2H, m), 1.4−1.2 (4H, m), 0.88 (3H,t, J=7 Hz)

IR (KBr) cm⁻¹:3304, 1644, 1077, 710

Elemental analysis (%): Calc'd for C₁₈H₂₃NO₂: C, 75.76; H, 8.12; N,4.91. Found: C, 75.77; H, 8.18; N, 5.06

EXAMPLE 27 2,5-Dimethylfuran-3-carboxy-(3-cyclohexylanilide)

Yield:52.7%

m.p.:113.0-114.5° C.

¹H NMR (CDCl₃) δ ppm: 7.48 (1H, m), 7.35 (1H, m), 7.28 (1H, b), 7.25(1H, t, J=8 Hz), 6.98 (1H, d, J=8 Hz), 6.1 (1H, s), 2.55 (3H, s),2.55−2.45 (1H, m), 2.25 (3H, s), 1,95−1.68 (5H, m), 1.55−1.15 (5H, m)

IR (KBr) cm⁻¹:3324, 1646, 1230, 1074, 791

Elemental analysis (%): Calc'd for C₁₉H₂₃NO₂: C, 76.74; H, 7.80; N,4.71. Found: C, 76.62; H, 7.78; N, 4.67

EXAMPLE 28 2,5-Dimethylfuran-3-carboxy(3-cyclopentylanilide)

Yield:35.9%

m.p.:92.0-93.0° C.

¹H NMR (CDCl₃) δ ppm: 7.45 (1H, m), 7.35 (1H, m), 7.25 (1H, b), 7.22(1H, t, J=8 Hz), 7.00 (1H, d, J=8 Hz), 6.1 (1H, s), 3.08−2.9 (1H, m),2.55 (3H, s), 2.25 (3H, s), 2.15−1.95 (2H, m), 1.9−1.5 (6H, m)

IR (KBr) cm⁻¹:3322, 1647, 1232, 1076, 700

Elemental analysis (%): Calc'd for C₁₈H₂₁NO₂: C, 76.30; H, 7.47; N,4.94. Found: C, 76.21; H, 7.56; N, 4.93

EXAMPLE 29 2,5-Dimethylfuran-3-carboxy(3-benzylanilide)

Yield:59.8%

m.p.:123.0-125.0° C.

¹H NMR (CDCl₃) δ ppm: 7.45 (1H, m), 7.38 (1H, m), 7.35−7.15 (7H, m),6.95 (1H, d, J=8 Hz), 3.98 (2H, s), 2.55 (3H, s), 2.25 (3H, s)

IR (KBr) cm⁻¹:3314, 1640, 1078, 777, 701

Elemental analysis (%): Calc'd for C₂₁H₁₉NO₂: C, 78.66; H, 6.27; N,4.59. Found: C, 77.76; H, 6.28; N, 4.55

REFERENTIAL EXAMPLE 1 Ethyl 2,5-Dimethylfuran-3-carboxylate

To a suspension of 2.4 g of sodium hydride (60% dispersion in mineraloil) in 10 ml of N,N-dimethylformamide (hereinafter, abbreviated as DMF)a solution of 6.5 ml of ethyl acetoacetate in 5 ml of DMF was addeddropwise with stirring under ice-cooling, and 5.97 ml of chloroacetonewere added dropwise thereto with stirring under ice-cooling. Afterstirring at room temperature for 3 hours, the reaction mixture waspoured into water and the aqueous mixture was extracted with ethylacetate. The extract was washed with a saturated aqueous solution ofsodium chloride and dried over anhydrous sodium sulfate. Afterdistilling off the solvent under reduced pressure, the residue wasdistilled in vacuo to give 8.01 g of ethyl αacetonitrile-acetoacetatehaving b.p. 105° C./2 mmHg in a 86% yield.

To a solution of the ester thus obtained in 20 ml of ethanol were added2 g of p-toluenesulfonic acid, and the resulting mixture was heatedunder reflux for 2 hours. The reaction mixture was allowed to cool toroom temperature and the solvent was distilled off under reducedpressure. The residue was dissolved in ethyl acetate and the solutionwas washed with a saturated aqueous solution of sodium chloride followedby drying over anhydrous magnesium sulfate. After distilling off thesolvent under reduced pressure, the residue was purified by columnchromatography through silica gel using a 10:1 mixture of n-hexane andethyl acetate as an eluent to give 5.14 g of ethyl2,5-dimethylfuran-3-carboxylate in a 71% yield.

REFERENTIAL EXAMPLE 2 2,5-Dimethylfuran-3-carboxylic acid

A mixture of 3.2 g of ethyl 2,5-dimethylfuran-3-carboxylate, 35 ml ofethanol and 20 ml of 2 N sodium hydroxide was stirred at roomtemperature for 1.5 hours followed by heating under reflux for an hour.After the reaction mixture was allowed to cool to room temperature, itwas concentrated under reduced pressure. The residue was dissolved inwater and acidified with diluted sulfuric acid. Precipitated crystalswere collected by filtration, washed with water and dried to give 2.27 gof 2,5-dimethylfuran-3-carboxylic acid in a 85% yield.

The compound having the general formula (I) mentioned above and thecomposition containing the compound (I) as the active ingredient, withwhich the present invention are concerned, can be employed by mixingwith carriers or, if necessary, with any other additives, followed bythe preparation of formulations usually employed such as oil solution,emulsifiable concentrate, solubilizer, paste, wettable powder, flowable,dry flowable, spray and paint, and then the formulation can be usedaccording to any known method for wood preservative treatment. As theadditives which are employed suitably to improve the property of theformulation and to strengthen the wood preserving effect, there may bementioned cationic, anionic and non-ionic surfactants, various highpolymer compounds such as methylcellulose and vinyl acetate resin andwater-repellents such as silicon oil and paraffin. It is needless to saythat combined use may be possible with other wood preservatives,fungicides and bateriocides including organic iodine compounds such asSanplas, IF-1000 and Troysan, azole compounds such as Propiconazole andTebuconazole, Thiabendazole, Dichlofluanid and quaternary ammonium saltcompounds; with insecticides including pyrethroids such as Permethrin,Etofenprox, Cypermethrin, Silaneophen, Tralomethrin, organic phosphorcompounds such as Chloropyrifos, Phoxim and Propetamphos, withImidacroprid; and with potentiators such asbi-(2,3,3,3-tetrachloropropyl) ether. An increased effect can beexpected by combined use in this manner. In a real case of application,through the content of the compound of the present invention can bechanged within a wide range depending on the formulation or on theobject, it may usually be suitable to use from 0.1 to 95 weight percent,preferably from 0.2 to 60 weight percent. These formulations areemployable in usual methods for wood treatment: for example, coating,dispersal, dipping treatment, mixing, impreganation, or mixing treatmentwith an adhesive.

Several formulation examples of the compound of the present inventionwill be shown below, in which it is needless to say that the combinationratio and the kind of additives can be changed widely (in thedescriptions below, part means weight part in all cases).

FORMULATION EXAMPLES OF THE WOOD PRESERVATIVES FORMULATION EXAMPLE 1Emulsifiable Concentrate

Twenty parts of the Compound of Example 20 were dissolved in 70 parts ofxylene, and then 10 parts of polyoxyethylene nonyl phenyl ether wereadded and mixed enough to obtain the emulsifiable concentrate.

Thus obtained emulsifiable concentrate is diluted with a suitable amountof water at use, and can be applied to a wood material to be treated bycoating, dipping or spraying, and in addition, employable by mixing withadhesives which are used for plywood, particle board and hardboard.

FORMULATION EXAMPLE 2 Oil Solution

Two parts of the Compound of Example 21 were added with 98 parts ofkerosene oil to obtain the oil solution.

Thus obtained oil solution can be applied to a wood material to betreated by spraying, coating, dipping or impregantion.

FORMULATION EXAMPLE 3 Coating Formulation

Ten parts of the Compound of Example 20, 20 parts of Barite dust, 10parts of vinyl resin, 25 parts of pine resin and 35 parts of xylene weremixed homogeneously to obtain the coating formulation.

FORMULATION EXAMPLE 4 Wettable Powder

Forty parts of the Compound of Example 22, 56 parts of clay, 3 parts ofsodium lauryl alcohol sulfonate and 1 part of polyvinyl, alcohol weremixed homogeneously in a mixer, and pulverized by use of a hammer-millto obtain the wettable powder.

TEST EXAMPLES OF WOOD PRESERVATION

The effectiveness of the wood preservative of the present invention willbe explained concretely by the following examples.

(1) According to the test method for wood preservation described in theJapan Industrial Standards [JIS A-9201 (1991)], each of the testcompounds was dissolved to a defined concentration in methanol. Thesolution was impregnated under a reduced pressure into a Sugi (Japanesecedar) sapwood (2×2×1) cm and then air-dried. Weathering test wasrepeated 10 times in which one cycle of the treatment was stirring inwater for 8 hours, and then heating for 16 hours at 60° C. The testmaterial was placed on the flora of Serpula lacrymans which had beenpreviously grown on a quartz sand medium (malt extract 2%, glucose 1%,peptone 0.3% and yeast 0.2%), and forcedly decayed at 20° C. for 12weeks. From the difference between the dry weight of the test materialbefore the test and that after test, the degree of decrease in weightwas obtained. Table 2 shows the results. The test was carried out by useof 9 samples for each condition, and the values shown in Table 2 are themean values calculated from 9 samples.

TABLE 2 Sample drugs Impregnant Mean weight decrease concentration (%)by decay (%) Example 20 0.01 0 0.005 0.1 Example 21 0.01 0 0.005 0Control compound 1 0.01 9.7 0.005 18.6 Without treatment 18.4 Controlcompound 1: 4-Chlorophenyl-3-iodopropargylformal Product of Nagase Co.,Ltd.: IF-1000

From the data shown above, the compound having the general formula (I)prevented decay of the wood samples due to wood-rotting fungi to asignificant extent.

(2) Each of 0.1 w/v % methanol solutions of the compound of the presentinvention and the control drug was impregnated into the test material [aSugi (Japanese cedar) sapwood, 2×2×0.5 cm] under a reduced pressure andthen air-dried. Weathering test was repeated twice in which one cycle ofthe treatment was washing (about 2 liter per minute supply) with waterfor 5 hours, and then heating for 19 hours at 60° C. After dry airsterilization, the test samples were prepared.

The test materials were placed on the flora of Coriolus versicolor whichis a lignin-decomposing fungus, and of Tryomyces palustris which is acellulose-decomposing fungus, and both of which are designated fungalspecies for assay of wood preservating effect. Both fungi had beenpreviously grown on an agar medium (malt extract 2%, glucose 1% andpeptone 0.5%). After the wood samples were forcedly deteriorated at 26°C. for 3 weeks, the effectiveness was determined from the degree ofhyphal growth on the test material and the presence or absence oflowered maximum crushing strength. Table 3 shows the result.

The wood preventive efficacy was judged by the following criteria.

+: No hyphal growth was observed on the test material, and no differencewas found in the maximum crushing strength from the healthy wood sample.

±: A little hyphal growth was observed on the test material, or a littledecrease was found in the maximum crushing strength.

−: Hyphal growth was observed on the test material, or clear decreasewas found in the maximum crushing strength.

TABLE 3 Test drug Coriolus versicolor Tyromyces palustris Example 1 ± −Example 2 − − Example 3 − − Example 4 − − Example 5 − − Example 6 + +Example 7 + − Example 8 ± − Example 9 − − Example 10 + − Example 11 + ±Example 12 ± ± Example 13 + + Example 14 + + Example 15 + − Example20 + + Example 21 + + Example 23 + + Example 24 + + Example 25 + +Example 26 + + Control compound 2 + + Without treatment − − Controlcompound 2: 3-Bromo-2,3-diiodo-2-propenylethylcarbonate Product ofSankyo Co., Ltd.: Sanplas

When the composition of the present invention is desired to be employed,the combination ratio may be suitably selected depending on the kind ofwood and the kind of wood material to be treated with the woodpreservative, or the means for treatment (for example, coating, dipping,dispersal, impregnation, mixing and mixing with an adhesive). Usually,the combination ratio of dimethylfurancarboxyanilide and any other woodpreservative may be from 240:1 to 1:35, preferably from 30:1 to 1:10,and more preferably from 5:1 to 1:5.

The content of the composition of the present invention may be changedwithin a wide range depending on the formulation. In general, thecontent may be from 0.1 to 95%, preferably from 0.2 to 60%, in theformulation.

Several formulation examples of the compound of the present inventionwill be shown below, in which it is needless to say that the combinationratio and the kind of additives can be changed widely.

FORMULATION EXAMPLES OF THE WOOD PRESERVATIVE COMPOSITION FORMULATIONEXAMPLE 1 Emulsifiable Concentrate

Ten parts of the Compound of Example 20 were dissolved in 30 parts ofSanplas and 50 parts of xylene, 10 parts of polyoxyethylene nonyl phenylether were then added and mixed enough to obtain the emulsifiableconcentrate.

Thus obtained emulsifiable concentrate is diluted with a suitable amountof water at the time of use, and can be applied to a wood material to betreated by coating, dipping or spraying, and in addition, employable bymixing with adhesives which are used for plywood, particle board andhardboard.

FORMULATION EXAMPLE 2 Oil Solution

Two parts of the compound of Example 21 and 1 part of troysan weredissolved in 96 parts of kerosene oil to obtain the oil solution.

FORMULATION EXAMPLE 3 Wettable Powder

Fifteen parts of the compound of Example 22, 25 parts of IF-1000, 56parts of clay, 3 parts of sodium lauryl alcohol sulfonate and 1 part ofpolyvinyl alcohol were mixed homogeneously in a mixer, and pulverized byuse of a hammer-mill to obtain the wettable powder.

The effect of the wood preservative composition of the present inventionwill be explained concretely by the following examples.

TEST EXAMPLES OF WOOD PRESERVATIVE COMPOSITIONS

Assay of minimum inhibitory concentration by the agar dilution method.

According to the agar dilution method, on sterilized media (potatodextrose agar medium; potato extract powder 0.4%, glucose 2%, agar 1.5%)prepared to contain certain concentrations of a test sample, flora(about 4 mm in diameter) of wood rotting fungi, Coriolus versicolor andTyromyces palustris, which has been cultured previously on the same kindof medium, were inoculated. After culture at 25° C. for 5 days, hyphalgrowth was observed to determine the minimum inhibitory concentration.

Whether there is any potentiation or not has been described in AppliedMicrobiology 9, 538-541 (1961) by F. C. Kull et al. The assay wascarried out according to the method usually employed.

Table 4 and FIGS. 1A to 1F show the results obtained by combination ofExample 20 with each of Sanplas, Troysan and IF-1000.

TABLE 4-1 MIC (ppm) of Example 20 combined with several other activeagents Test (Combined ratio) fungus Example 20 A Example 20 + A Example20:A Coriolus 2.5 15 1.30 + 3.0    (1:2.3) Versicolor 0.8 + 5.0  (1:6.3) 0.4 + 9.0   (1:22.5) Tyromyces 200 25 110.0 + 5.0  (22:1) Palustris 70.0 + 9.0  (7.8:1)   40.0 + 14.0 (2.9:1)   A: Sanplas

TABLE 4-2 MIC (ppm) of Example 20 combined with several other activeagents Test (Combined ratio) fungus Example 20 B Example 20 + B Example20:B Coriolus 2.5 25 1.25 + 5.0  (1:4) Versicolor 0.8 + 7.5   (1:9.4) 0.4 + 12.5   (1:31.3) Tyromyces 200 2.5 120.0 + 0.6  (200:1)  Palustris80.0 + 1.0  (80:1)  40.0 + 1.5  (26.7:1)   B: Troysan

TABLE 4-3 MIC (ppm) of Example 20 combined with several other activeagents Test (Combined ratio) fungus Example 20 C Example 20 + C Example20:C Coriolus 2.5 6 1.25 + 1.2  (1.0:1)   Versicolor 0.8 + 1.8   (1:2.3)0.5 + 3.0 (1:6) Tyromyces 200 2 120.0 + 0.5  (240:1)  Palustris 80.0 +0.8  (100:1)  40.0 + 1.2  (33:1)  C: IF-1000

Then, the same test as above was carried out for Example 21. Table 5 andFIGS. 2A to 2F show the result.

TABLE 5-1 MIC (ppm) of Example 21 combined with several other activeagents Test (Combined ratio) fungus Example 21 A Example 21 + A Example21:A Coriolus 10.0 15 6.0 + 3.0 (2:1) Versicolor 3.5 + 5.0   (1:1.4)2.0 + 8.0 (1:4) Tyromyces 200 25 120.0 + 5.0  (24:1)  Palustris 75.0 +9.0  (8.3:1)   40.0 + 15.0 (2.7:1)   A: Sanplas

TABLE 5-2 MIC (ppm) of Example 21 combined with several other activeagents Test (Combined ratio) fungus Example 21 B Example 21 + B Example21:B Coriolus 10.0 25 5.5 + 5.0 (1.1:1)   Versicolor 3.0 + 8.0   (1:2.7) 1.5 + 12.5   (1:8.3) Tyromyces 200 2.5 120.0 + 0.7  (171.4:1)   Palustris 90.0 + 1.0  (90:1)  40.0 + 1.75 (22.9:1)   B: Troysan

TABLE 5-3 MIC (ppm) of Example 21 combined with several other activeagents Test (Combined ratio) fungus Example 21 C Example 21 + C Example21:C Coriolus 10.0 6 6.0 + 1.6 (3.6:1)   Versicolor 4.0 + 2.4 (1.7:1)  2.0 + 3.6   (1:1.8) Tyromyces 200 2 120.0 + 0.5  (240:1)  Palustris90.0 + 1.0  (90:1)  40.0 + 1.4  (28.6:1)   C: IF-1000

Each of the minimum inhibitory concentration curves shown in FIGS. 1A to1F and FIGS. 2A to 2F lies under the diagonal line shown by broken line.

This data exhibits that the furancarboxyanilide derivative potentiatesthe effect of each of Sanplas, Troysan and IF-1000 by combination.

We claim:
 1. A dimethylfurancarboxyanilide compound of the formula (I):

wherein R¹ or R² or both R¹ and R² are a benzyl group selected from thegroup consisting of benzyl, 2-methylbenzyl, 2,4-dimethylbenzyl,2-chlorobenzyl, 4-methoxybenzyl and 4-ethoxybenzyl.
 2. Thedimethylfurancarboxyanilide compound of claim 1, wherein the compound is2,5-dimethylfuran-3-carbonyl(3-benzylanilide).
 3. Thedimethylfurancarboxyanilide compound of claim 1, wherein the compound is2,5-dimethylfuran-3-carboxy[3-(4-methoxybenzyl)anilide].
 4. Adimethylfurancarboxyanilide compound which is2,5-dimethylfuran-3-carboxy(3-isopropylanilide).
 5. Adimethylfurancarboxyanilide compound which is2,5-dimethylfuran-3-carboxy(3-isopropyloxymethylanilide).
 6. Adimethylfurancarboxyanilide compound which is2,5-dimethylfuran-3-carboxy[3-(2-methoxycarbonylvinyl)anilide].